Pharmacokinetics and pharmacodynamics of peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis in the randomized ADVANCE study.
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Hu X, Cui Y, White J, Zhu Y, Deykin A, Nestorov I, Hung S
Pharmacokinetics and pharmacodynamics of peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis in the randomized ADVANCE study.
Br J Clin Pharmacol. 2015 Mar;79(3):514-22. doi: 10.1111/bcp.12521.
- PubMed ID
- 25265472 [ View in PubMed]
- Abstract
AIMS: To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of subcutaneous peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis (RRMS) in the phase 3 ADVANCE study (n = 1512). METHODS: During year 1, patients were randomized (1:1:1) to placebo or peginterferon beta-1a 125 mug every 2 or 4 weeks. After year 1, patients randomized to placebo were re-randomized to 125 mug peginterferon beta-1a administered every 2 weeks or every 4 weeks for year 2. Patients randomized to peginterferon beta-1a in year 1 remained on the same dosing regimen in year 2. Intensive blood samples for PK and PD (neopterin elevation; a biomarker of pharmacological activity induced by interferon beta-1a) measurements were collected from 44 patients pre-dosing and at intervals over 240 h post-dosing at weeks 4 and 24. Sparse samples were collected from all patients after each dosing at weeks 4, 12, 24, 56 and 84. RESULTS: The PK profile of peginterferon beta-1a did not change over time or between dosing regimens. No accumulation was observed. Peak serum concentrations were reached 1-1.5 days post-dosing, with a mono-phasic decline and a median half-life of approximately 2-3 days. Dosing every 2 weeks provided approximately two-fold greater monthly cumulative area under the curve than every 4 weeks. Neopterin elevation was sustained for 10-14 days following each dose, indicating doubled cumulative duration of pharmacological activity for dosing every 2 weeks vs. every 4 weeks. CONCLUSIONS: These PK/PD profiles potentially explain the enhanced efficacy of dosing every 2 weeks in patients with RRMS.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Peginterferon beta-1a Interferon alpha/beta receptor 1 Protein Humans UnknownActivatorDownregulatorDetails